In Homo sapiens, the apoptosis-inducing factor (AIF) family is represented by three different proteins, known as AIF, AMID and AIFL, that have in common the mitochondrial localisation in healthy cells, the presence of FAD- and NADH-dependent domains involved in an -albeit yet not well understood- oxidoreductase function and their capability to induce programmed cell death. AIF is the best characterised family member, while the information about AMID and AIFL is much scarcer. Nonetheless, available data support different roles as well as mechanisms of action of their particular apoptogenic and redox domains regarding both pro-apoptotic and anti-apoptotic activities. Moreover, diverse cellular functions, to date far from fully clarified, are envisaged for the transcripts corresponding to these three proteins. Here, we review the so far available knowledge on the moonlighting human AIF family from their molecular properties to their relevance in health and disease, through the evaluation of their potential cell death and redox functions in their different subcellular locations. This picture emerging from the current knowledge of the AIF family envisages its contribution to regulate signalling and transcription machineries in the crosstalk among mitochondria, the cytoplasm and the nucleus.

中文翻译：

---

凋亡诱导因子家族：线粒体和细胞核之间串扰中的兼职蛋白


在智人中，凋亡诱导因子 (AIF) 家族由三种不同的蛋白质代表，即 AIF、AMID 和 AIFL，它们的共同点是健康细胞中的线粒体定位，以及涉及 FAD 和 NADH 依赖性结构域的存在尽管尚未充分了解氧化还原酶的功能及其诱导程序性细胞死亡的能力。 AIF 是最具特征的家族成员，而关于 AMID 和 AIFL 的信息则要少得多。尽管如此，现有数据支持其特定的凋亡和氧化还原域在促凋亡和抗凋亡活性方面的不同作用和作用机制。此外，迄今为止还远未完全阐明的不同细胞功能被设想为与这三种蛋白质相对应的转录物。在这里，我们通过评估其不同亚细胞位置的潜在细胞死亡和氧化还原功能，回顾了迄今为止关于兼职人类 AIF 家族的现有知识，从其分子特性到其与健康和疾病的相关性。从目前对 AIF 家族的了解中得出的这张图设想了它对调节线粒体、细胞质和细胞核之间的串扰中的信号传导和转录机制的贡献。